Amphetamine, administered at low-moderate doses, enhances physical performance and endurance, while high doses produce muscle weakness and paralysis. This project has been investigating these phenomena in rodents, in vivo and in vitro. Amphetamine has been found to increase treadmill running times at low doses, while reducing treadmill and rotarod performances at high doses. Similarly, low and high concentrations of amphetamine stimulate and block, respectively, the contractions of isolated nerve-stimulated skeletal muscle. Studies are being conducted to ascertain the mechanisms responsible for these biphasic effects. It is suggested that the salutary effects of amphetamine on physical performance and endurance may result, at least in part, from the effects of this drug on neuromuscular transmission.